Many diagnostic and therapeutic procedures provide the step of percutaneously introducing instruments and/or catheters through vascular entry sites. To this purpose, introducer sheaths are used, i.e. substantially cylindrical valved cannulas, which are removed only at the end of the procedure.
At the moment of the removal of the introducer sheath, the entry site, i.e. a hole in the wall of the artery, remains open and must be immediately closed to avoid bleeding. For closing the hole and stopping the blood outflow at the removal of the introducer sheath, a well-known technique provides exerting a compression force at the entry site, first manually and then by means of a bandage or by application of a weight. The compression force causes also a local reduction of the arterial blood pressure proximate to the entry site, which first allows natural haemostasis process to start, and which then avoids that sudden blood pressure changes or movements of the patient causes the entry site to open again. Once bleeding has been stopped, the repair of the entry site is completed within a few days. For instance, in the case of a femoral entry site of a patient who has normal coagulation parameters, the closing treatment of the entry site by a means of compression usually lasts between 8 and 12 hours, during which the patient must remain motionless.
Complications may sometimes arise such as bleeding, hematomas, pseudoaneurysms, in particular in the case of patients whose blood hardly coagulate due to a disease or to an a anticoagulation treatment, or in the case of patients who have a vascular prosthesis (by-pass) at the inguinal region.
In some cases, even by prolonging the compression the entry site cannot be closed, and a surgical treatment is necessary, which may involve further risks, discomfort, prolonged period in bed and resources waste. Furthermore, in case of obese patients, the adipose layer that is located between the skin and the vascular entry site reduces the efficiency of the compression.
Moreover, an entry site on a vascular prosthesis that is made of plastic (Dacron, PTFE, etc.) cannot heal by the natural repair processes of an artery, and, on the contrary, it can only be closed by formation of a true plug made of blood that, after flowing out of the opening, coagulates through the tissues that surround the prosthesis, under the assistance of the compression force. In this case, therefore, the risk that bleeding may start again when the compression force is released is much higher, which suggests to avoid entry sites of vascular prosthesis; on the other hand, this is particularly desirable when dilatative or stenosing diseases have to be solved upstream or downstream of the prosthesis.
Systems are also known for closing percutaneous entry sites, which comprise a suture means and/or a mechanical closing means, such as grafts or plaques, which may be associated with a haemostatic liquid. Such systems reduce the average treatment time. However, the introduction of objects into the blood vessels may cause thrombosis related ischemia, embolism, arterial wall laceration, sensitization, allergic reaction. Furthermore, the mechanical closure devices require a highly skilled operator, and/or the work of further assistant operators. Therefore, these techniques do not provide a valid alternative to the traditional techniques.
Systems are also known for closing the entry site of an introducer sheath with exclusive use of a haemostatic liquid, in particular collagen, to form clots that are involved in a natural coagulation mechanisms; however, the haemostasis process is slow, and complications may arise such as blood suffusion, bleeding, pseudoaneurysms.
Quickly setting haemostatic liquids are also known, which would be well-suited for forming a strong and flexible closure at the entry site. Liquid of this kind, such as internal use surgical glues, have not been used so far for closing percutaneous vascular entry sites, since:                for injecting a haemostatic liquid in a narrow space like that is available at a percutaneous access, it is preferable to use small cross section ducts, to limit the amount of liquid to be used and to avoid the production of hardened lumps under the skin; similar ducts are easily closed by the quickly-setting haemostatic liquids that quickly harden by reacting with blood, lymph or other biological material that enters the duct during the puncture, which makes the injection impossible to carry out;        it is very difficult to release a quick setting haemostatic liquid in a pure state in an operation region where blood under pressure is present. The methods that use quick setting surgical glues provide a dilution of the glue, but this prolongs the hardening time;        with well known techniques, and also under echographic control, it is difficult to release such pure quick setting haemostatic liquid proximate to a vascular entry site without the risk of injecting it into the blood vessel, with such complications as thrombosis or embolisms. For this reason, in order to use a quick setting haemostatic liquid, and at the same time to avoid an echographic control, it is important to establish as precisely as possible the position of the point where the liquid must be released.        
The echographic control may not be always available when this kind of intervention is performed, because it requires experienced operators and in any case it requires more than one operator for closing the entry site.
To this purpose, in EP0941697 a device is described for bringing a haemostatic substance proximate to a percutaneous entry site. The device comprises a cylindrical body that is coaxially coupled to the introducer sheath that slides along it until a “sensation” is felt that the device has reached the artery. Then the haemostatic substance is released. The device is mounted on the introducer sheath before positioning it in the blood vessel; therefore, it prevents the use of the whole length of the introducer sheath, which obliges a portion of the introducer sheath to be left outside of the skin, differently from what happens in the normal procedure. This causes an unsteady positioning of the introducer sheath, which is particularly critical in the case of obese patients, where the distance between the skin and the blood vessel is higher than in normal patients. Furthermore, the large transversal size of the device hinders the movement through the tissues, and “digs” an enlarged space about the introducer sheath in which both the released haemostatic liquid and the blood can accumulate without contributing to the entry site occlusion. In any case, the device is not adapted to treat a quick-setting liquid, because the delivery mouth may be easily clogged.
Various systems have been proposed to provide a liquid that is adapted is to make an occlusion in an operation region.
In particular the device of US2008/45700 is adapted to treat bleeding diseases, for example, in the stomach and in the intestine, but it cannot be used neither for an endovascular intervention, nor for closing an arterial entry site. Due to its high reactivity, a cyanoacrylate material would immediately polymerize when brought into contact with the blood, which would reduce the passage through the catheter, or even clog it, in such a way that the release of a significant amount of surgical glue would be impossible.
US patent application 2001/000616 relates to a method for applying a blood-based pro-coagulating substance proximate to a vascular entry site through a hole of a catheter to be inserted through an introducer sheath. For positioning the hole immediately out of the artery, the operator slowly withdraws the catheter until the blood stops flowing out of the distal end of it. This is a rough method, by which the risk may arise of injecting the procoagulating substance into the vessel; for the same reason, the method and the apparatus cannot be used to safely release surgical glues, which are not cited in the patent application.
International patent application WO 02/089675 relates to a device and to a method for blocking an arterial entry site of a patient who has been treated with anticoagulant therapy. This invention relates however to the use of blood that is taken from the patient itself and is treated with a substance that is an antagonists of the anticoagulant treatment, whereas it does not deal with surgical glues or similar liquids. Furthermore, the document does not provide precise indications about the way the liquid is supplied at the entry site. In any case, the device cannot be used to release a quick setting surgical glue proximate to an entry site, because the glue would come into contact too early with the nearby biological fluids which would block the device; furthermore, it does not allow an operator to determine the point of delivery, unless an echographic control is provided.
U.S. Pat. No. 3,548,825 relates to a syringe for injecting a mixture of two components that are contained in respective receptacles of the syringe, which allows mixing the liquids at the moment of the injection. Similarly to any well-known syringe, a similar device does not allow providing a quick setting. in particular of a haemostatic liquid in a pure state, at an entry site or in an is operation region of an endovascular surgery.
Concerning the endovascular surgery, such as an embolization of arterial or venous districts, or the treatment of arterial walls dissections, the problem often arises of covering a long distance between the entry site, which is normally made in the artery of the arm or in the femoral artery, and the operation region. When the use is desirable of a pure quick setting surgical glue, which would have a maximum efficiency and application speed, the problem arises of conveying the glue through a long duct, and of preventing at the same time any risks of contact between the glue and the blood until the remote vascular district is reached where the intervention must be made.